Inclusion of unexposed clusters improves the precision of fixed effects analysis of stepped-wedge cluster randomized trials with binary and count outcomes.

Abstract

Background: The fixed effects model is a useful alternative to the mixed effects model for analyzing stepped-wedge cluster randomized trials (SW-CRTs). It controls for all time-invariant cluster-level confounders and has proper control of type I error when the number of clusters is small. While all clusters in a SW-CRT are typically designed to crossover from the control to receive the intervention, some trials can end with unexposed clusters (clusters that never receive the intervention), such as when a trial is terminated early due to safety concerns. It was previously unclear whether unexposed clusters would contribute to the estimation of the intervention effect in a fixed effects analysis. However, recent work has demonstrated that including an unexposed cluster can improve the precision of the intervention effect estimator in a fixed effects analysis of SW-CRTs with continuous outcomes. Still, SW-CRTs are commonly designed with binary outcomes and it is unknown if those previous results extend to SW-CRTs with non-continuous outcomes.

Methods: In this article, we mathematically prove that the inclusion of unexposed clusters improves the precision of the fixed effects intervention effect estimator for SW-CRTs with binary and count outcomes. We then explore the benefits of including an unexposed cluster in simulated datasets with binary or count outcomes and a real palliative care data example with binary outcomes.

Results: The simulations show that including unexposed clusters leads to tangible improvements in the precision, power, and root mean square error of the intervention effect estimator. The inclusion of the unexposed cluster in the SW-CRT of a novel palliative care intervention with binary outcomes yielded smaller standard errors and narrower 95% Wald Confidence Intervals.

Conclusions: In this article, we demonstrate that the inclusion of unexposed clusters in the fixed effects analysis can lead to the improvements in precision, power, and RMSE of the fixed effects intervention effect estimator for SW-CRTs with binary or count outcomes.